{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T16:50:21Z","timestamp":1781110221224,"version":"3.54.1"},"reference-count":38,"publisher":"National Academy of Sciences","issue":"15","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2013,4,9]]},"abstract":"<jats:p>\n                    To define genetic lesions driving leukemia, we targeted cre-dependent Sleeping Beauty (SB) transposon mutagenesis to the blood-forming system using a hematopoietic-selective\n                    <jats:italic>vav 1 oncogene<\/jats:italic>\n                    (\n                    <jats:italic>vav1<\/jats:italic>\n                    ) promoter. Leukemias of diverse lineages ensued, most commonly lymphoid leukemia and erythroleukemia. The inclusion of a transgenic allele of\n                    <jats:italic>Janus kinase 2<\/jats:italic>\n                    (\n                    <jats:italic>JAK2<\/jats:italic>\n                    )\n                    <jats:italic>V617F<\/jats:italic>\n                    resulted in acceleration of transposon-driven disease and strong selection for erythroleukemic pathology with transformation of bipotential erythro-megakaryocytic cells. The genes encoding the E-twenty-six (ETS) transcription factors Ets related gene (Erg) and Ets1 were the most common sites for transposon insertion in SB-induced\n                    <jats:italic>JAK2V617F<\/jats:italic>\n                    -positive erythroleukemias, present in 87.5% and 65%, respectively, of independent leukemias examined. The role of activated\n                    <jats:italic>Erg<\/jats:italic>\n                    was validated by reproducing erythroleukemic pathology in mice transplanted with fetal liver cells expressing\n                    <jats:italic>translocated in liposarcoma<\/jats:italic>\n                    (\n                    <jats:italic>TLS<\/jats:italic>\n                    )\n                    <jats:italic>-ERG<\/jats:italic>\n                    , an activated form of ERG found in human leukemia. Via application of SB mutagenesis to\n                    <jats:italic>TLS-ERG<\/jats:italic>\n                    \u2013induced erythroid transformation, we identified multiple loci as likely collaborators with activation of\n                    <jats:italic>Erg<\/jats:italic>\n                    .\n                    <jats:italic>Jak2<\/jats:italic>\n                    was identified as a common transposon insertion site in\n                    <jats:italic>TLS-ERG<\/jats:italic>\n                    \u2013induced disease, strongly validating the cooperation between\n                    <jats:italic>JAK2V617F<\/jats:italic>\n                    and transposon insertion at the\n                    <jats:italic>Erg<\/jats:italic>\n                    locus in the\n                    <jats:italic>JAK2V617F<\/jats:italic>\n                    -positive leukemias. Moreover, loci expressing other regulators of signal transduction pathways were conspicuous among the common transposon insertion sites in\n                    <jats:italic>TLS-ERG<\/jats:italic>\n                    \u2013driven leukemia, suggesting that a key mechanism in erythroleukemia may be the collaboration of lesions disturbing erythroid maturation, most notably in genes of the\n                    <jats:italic>ETS<\/jats:italic>\n                    family, with mutations that reduce dependence on exogenous signals.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1304234110","type":"journal-article","created":{"date-parts":[[2013,3,27]],"date-time":"2013-03-27T20:28:38Z","timestamp":1364416118000},"page":"6091-6096","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":19,"title":["Transposon mutagenesis reveals cooperation of ETS family transcription factors with signaling pathways in erythro-megakaryocytic leukemia"],"prefix":"10.1073","volume":"110","author":[{"given":"Jian Zhong","family":"Tang","sequence":"first","affiliation":[{"name":"The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine L.","family":"Carmichael","sequence":"additional","affiliation":[{"name":"The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia;"},{"name":"Departments of bMedical Biology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Shi","sequence":"additional","affiliation":[{"name":"The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia;"},{"name":"Computing and Information Systems, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald","family":"Metcalf","sequence":"additional","affiliation":[{"name":"The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia;"},{"name":"Departments of bMedical Biology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley P.","family":"Ng","sequence":"additional","affiliation":[{"name":"The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia;"},{"name":"Departments of bMedical Biology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig D.","family":"Hyland","sequence":"additional","affiliation":[{"name":"The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy A.","family":"Jenkins","sequence":"additional","affiliation":[{"name":"Methodist Hospital Research Institute, Houston, TX 77030;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neal G.","family":"Copeland","sequence":"additional","affiliation":[{"name":"Methodist Hospital Research Institute, Houston, TX 77030;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viive M.","family":"Howell","sequence":"additional","affiliation":[{"name":"Kolling Institute of Medical Research, University of Sydney, St. Leonards, NSW 2065, Australia; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhizhuang Joe","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gordon K.","family":"Smyth","sequence":"additional","affiliation":[{"name":"The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia;"},{"name":"Mathematics and Statistics, University of Melbourne, Parkville, VIC 3010, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin T.","family":"Kile","sequence":"additional","affiliation":[{"name":"The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia;"},{"name":"Departments of bMedical Biology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Warren S.","family":"Alexander","sequence":"additional","affiliation":[{"name":"The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia;"},{"name":"Departments of bMedical Biology,"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2013,3,26]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2647"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2916"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-09-1135"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(04)00022-6"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-05-091579"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.22063"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2011.05.014"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrurol.2009.127"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1586\/ehm.10.62"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.5858\/2009-0350-RA.1"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-03-344739"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1617"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.2009211"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-09-242107"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-05-0147"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/377635a0"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.2174\/138955708785909934"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.1987.250"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.3457468"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2012.02.013"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.5.3.369"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1213454109"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.14.8239"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4401811"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1006\/bcmd.2002.0595"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1186\/1742-4690-5-99"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0609.2011.01586.x"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-07-365320"},{"key":"e_1_3_3_29_2","first-page":"1","article-title":"Vav1 in hematologic neoplasms, a mini review","volume":"2","author":"Oberley MJ","year":"2012","unstructured":"MJ Oberley, DS Wang, DT Yang, Vav1 in hematologic neoplasms, a mini review. 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